Transcriptional noise

Transcriptional noise is a primary cause of the variability (noise) in gene expression occurring between cells in isogenic populations (see also cellular noise) .[1] A proposed source of transcriptional noise is transcriptional bursting[2][3][4] although other sources of heterogeneity, such as unequal separation of cell contents at mitosis are also likely to contribute considerably.[5] Bursting transcription, as opposed to simple probabilistic models of transcription, reflects multiple states of gene activity, with fluctuations between states separated by irregular intervals, generating uneven protein expression between cells. Noise in gene expression can have tremendous consequences on cell behaviour, and must be mitigated or integrated. In certain contexts, such as the survival of microbes in rapidly changing stressful environments, or several types of scattered differentiation, the variability may be essential.[6] Variability also impacts upon the effectiveness of clinical treatment, with resistance of bacteria to antibiotics demonstrably caused by non-genetic differences.[7] Variability in gene expression may also contribute to resistance of sub-populations of cancer cells to chemotherapy.[8]

Notes

  1. ↑ Raj, A; Van Oudenaarden, A (2008). "Nature, nurture, or chance: stochastic gene expression and its consequences". Cell. 135 (2): 216–26. doi:10.1016/j.cell.2008.09.050. PMC 3118044Freely accessible. PMID 18957198.
  2. ↑ Golding, I; Paulsson, J; Zawilski, SM; Cox, EC (2005). "Real-time kinetics of gene activity in individual bacteria". Cell. 123 (6): 1025–36. doi:10.1016/j.cell.2005.09.031. PMID 16360033.
  3. ↑ Chubb, JR; Trcek, T; Shenoy, SM; Singer, RH (2006). "Transcriptional pulsing of a developmental gene". Current Biology. 16 (10): 1018–25. doi:10.1016/j.cub.2006.03.092. PMID 16713960.
  4. ↑ Raj, A; Peskin, CS; Tranchina, D; Vargas, DY; Tyagi, S (2006). "Stochastic mRNA synthesis in mammalian cells". PLoS Biology. 4 (10): e309. doi:10.1371/journal.pbio.0040309. PMC 1563489Freely accessible. PMID 17048983.
  5. ↑ Huh, D.; Paulsson, J. (2010). "Non-genetic heterogeneity from stochastic partitioning at cell division". Nature Genetics. 43 (2): 95–100. doi:10.1038/ng.729. PMC 3208402Freely accessible. PMID 21186354.
  6. ↑ Losick, R.; Desplan, C. (2008). "Stochasticity and cell fate". Science. 320 (5872): 65–68. Bibcode:2008Sci...320...65L. doi:10.1126/science.1147888. PMC 2605794Freely accessible. PMID 18388284.
  7. ↑ Lewis, K. (2010). "Persister Cells". Annual Review of Microbiology. 64: 357–372. doi:10.1146/annurev.micro.112408.134306. PMID 20528688.
  8. ↑ Sharma, S. V.; Lee, D. Y.; Li, B.; Quinlan, M. P.; Takahashi, F.; Maheswaran, S.; McDermott, U.; Azizian, N.; Zou, L.; Fischbach, M. A.; Wong, K. K.; Brandstetter, K.; Wittner, B.; Ramaswamy, S.; Classon, M.; Settleman, J. (2010). "A chromatin-mediated reversible drug tolerant state in cancer cell subpopulations". Cell. 141 (1): 69–80. doi:10.1016/j.cell.2010.02.027. PMC 2851638Freely accessible. PMID 20371346.
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